Infections with numerous viruses result in profound alterations in the immune system. The goals of this project have been to determine how retroviruses affect immune cell interactions and growth. Studies of mice infected with murine leukemia viruses (MuLV) that induce a severe immunodeficiency syndrome, MAIDS, demonstrated that interferon (IFN) was required for normal progression of disease. To understand IFN signaling in greater depth, we have studied mice with a null mutation of ICSBP, a transcriptional factor of the IFN regulatory factor (IRF) family induced by IFN. These studies have demonstrated a prominent role for IRF family members in regulating normal and aberrant hemopoiesis. Studies of ICSBP-deficient mice demonstrated that they develop a myeloproliferative disease that resembles chronic myelogenous leukemia in humans. We have shown that the bases for this accumulative disease include increased proliferation of myeloid precursor cells as well as resistance to spontaneous or drug?induced cell death. As part of our efforts to understand hematopoietic differentiation, we have prepared and sequenced libraries from normal bone marrow stem cells, mobilized normal blood stem cells and stem cells from a patient with chronic myelogenous leukemia. - Immunodeficiency, interferon, apoptosis, differentiation, interferon consensus sequence binding protein - Human Subjects